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21.
Heeyoung Seok Haejeong Lee Eun-Sook Jang Sung Wook Chi 《Cellular and molecular life sciences : CMLS》2018,75(5):797-814
RNA interference (RNAi) has been widely adopted to repress specific gene expression and is easily achieved by designing small interfering RNAs (siRNAs) with perfect sequence complementarity to the intended target mRNAs. Although siRNAs direct Argonaute (Ago), a core component of the RNA-induced silencing complex (RISC), to recognize and silence target mRNAs, they also inevitably function as microRNAs (miRNAs) and suppress hundreds of off-targets. Such miRNA-like off-target repression is potentially detrimental, resulting in unwanted toxicity and phenotypes. Despite early recognition of the severity of miRNA-like off-target repression, this effect has often been overlooked because of difficulties in recognizing and avoiding off-targets. However, recent advances in genome-wide methods and knowledge of Ago–miRNA target interactions have set the stage for properly evaluating and controlling miRNA-like off-target repression. Here, we describe the intrinsic problems of miRNA-like off-target effects caused by canonical and noncanonical interactions. We particularly focus on various genome-wide approaches and chemical modifications for the evaluation and prevention of off-target repression to facilitate the use of RNAi with secured specificity. 相似文献
22.
Jae Eun Park Byoung Chul Park Hyun-A Kim Mina Song Sung Goo Park Do Hee Lee Hyeoung-Joon Kim Hyung-Kyoon Choi Jong-Tae Kim Sayeon Cho 《Cellular and molecular life sciences : CMLS》2010,67(15):2619-2629
Apoptosis signal-regulating kinase 1 (ASK1), a member of the MAP kinase kinase kinase, is activated by several death stimuli and is tightly regulated by several mechanisms such as interactions with regulatory proteins and post-translational modifications. Here, we report that dual-specificity phosphatase 13A (DUSP13A) functions as a novel regulator of ASK1. DUSP13A interacts with the N-terminal domain of ASK1 and induces ASK1-mediated apoptosis through the activation of caspase-3. DUSP13A enhances ASK1 kinase activity and thus its downstream factors. Small interfering RNA (siRNA) analyses show that knock-down of DUSP13A in human neuroblastoma SK-N-SH cells reduces ASK1 kinase activity. The phosphatase activity of DUSP13A is not required for the regulation of ASK1. This regulatory action of DSUP13 on ASK1 activity involves competition with Akt1, a negative regulator of ASK1, for binding to ASK1. Taken together, this study provides novel insights into the role of DUSP13A in the precise regulation of ASK1. 相似文献
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24.
Leonard DC Filippenko AV Ganeshalingam M Serduke FJ Li W Swift BJ Gal-Yam A Foley RJ Fox DB Park S Hoffman JL Wong DS 《Nature》2006,440(7083):505-507
An important and perhaps critical clue to the mechanism driving the explosion of massive stars as supernovae is provided by the accumulating evidence for asymmetry in the explosion. Indirect evidence comes from high pulsar velocities, associations of supernovae with long-soft gamma-ray bursts, and asymmetries in late-time emission-line profiles. Spectropolarimetry provides a direct probe of young supernova geometry, with higher polarization generally indicating a greater departure from spherical symmetry. Large polarizations have been measured for 'stripped-envelope' (that is, type Ic; ref. 7) supernovae, which confirms their non-spherical morphology; but the explosions of massive stars with intact hydrogen envelopes (type II-P supernovae) have shown only weak polarizations at the early times observed. Here we report multi-epoch spectropolarimetry of a classic type II-P supernova that reveals the abrupt appearance of significant polarization when the inner core is first exposed in the thinning ejecta (approximately 90 days after explosion). We infer a departure from spherical symmetry of at least 30 per cent for the inner ejecta. Combined with earlier results, this suggests that a strongly non-spherical explosion may be a generic feature of core-collapse supernovae of all types, where the asphericity in type II-P supernovae is cloaked at early times by the massive, opaque, hydrogen envelope. 相似文献
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对用仿形磨削方法磨削硬质合金可转位刀片周边的仿形凸轮机构进行了运动学分析,根据凸轮机构的运动学特性开发出一套设计和绘制仿形凸轮的CAD和CAG软件,采用该软件可以省去大量的繁复计算与绘图工作量,缩短设计制造周期,实现设计、绘图自动化。 相似文献
27.
Energy dissipators, isolated-resistant and specific structural forms for earthquake resistance are popular topics in the research to improve shock-resistance. In this work, experimental methods were used to investigate the property of low yield strength steel. Carbon content in LYS material is lower than that in other steels; the ultimate stress is three times the yield stress. The ultimate elongation rate is about 62% and the ductility is 2-3 times that of A36 steel. In order to overcome some defects of ordinary use metallic dampers, the mechanical characteristic of low yield strength steel is used to develop added damping and stiffness for rhombic steel plate absorber. Test of the energy dissipation behavior for this newly developed device indicated that LYS could stably dissipate or absorb the input energy of earthquake. Then, the analytical model for the hysteretic behavior of this new device is proposed. Comparison of experimental data and numerical simulation results showed that this analytical model is suitable for simulating the hysteretic energy behavior of this new device. 相似文献
28.
Evolution of microRNA genes by inverted duplication of target gene sequences in Arabidopsis thaliana 总被引:8,自引:0,他引:8
Allen E Xie Z Gustafson AM Sung GH Spatafora JW Carrington JC 《Nature genetics》2004,36(12):1282-1290
29.
Sung BJ Hwang KY Jeon YH Lee JI Heo YS Kim JH Moon J Yoon JM Hyun YL Kim E Eum SJ Park SY Lee JO Lee TG Ro S Cho JM 《Nature》2003,425(6953):98-102
Phosphodiesterases (PDEs) are a superfamily of enzymes that degrade the intracellular second messengers cyclic AMP and cyclic GMP. As essential regulators of cyclic nucleotide signalling with diverse physiological functions, PDEs are drug targets for the treatment of various diseases, including heart failure, depression, asthma, inflammation and erectile dysfunction. Of the 12 PDE gene families, cGMP-specific PDE5 carries out the principal cGMP-hydrolysing activity in human corpus cavernosum tissue. It is well known as the target of sildenafil citrate (Viagra) and other similar drugs for the treatment of erectile dysfunction. Despite the pressing need to develop selective PDE inhibitors as therapeutic drugs, only the cAMP-specific PDE4 structures are currently available. Here we present the three-dimensional structures of the catalytic domain (residues 537-860) of human PDE5 complexed with the three drug molecules sildenafil, tadalafil (Cialis) and vardenafil (Levitra). These structures will provide opportunities to design potent and selective PDE inhibitors with improved pharmacological profiles. 相似文献
30.
Two new species of the family Canuellidae Lang, 1944, Scottolana jasani sp. nov. collected from Gusipo Beach, Korea and S. huysi sp. nov. from Kata Beach, Phuket Island, Thailand, are described. So far 14 species are currently known in the genus, of which only two, S. bulbifera from Russia, China, and Korea, and S. geei from China, have been reported from Asia. The new species, Scottolana jasani sp. nov. and S. huysi sp. nov., belong to the longipes-group, defined by the presence of two postgenital segments in the female, and caudal ramus with a proximal hook-like inner projection. Scottolana jasani sp. nov. closely resembles S. geei. However, it is easily distinguished by the following characters: (1) number of segments of antennal exopod (8 in the new species, but 9 in S. geei); (2) setae I, and II of caudal ramus; (3) shape of genital field in both sexes; (4) segmentation of mandibular exopod; and (5) spinular ornamentation of endopod-2 in P1. Scottolana huysi sp. nov. is also closely related to S. geei. However, it is unique and different from S. geei by (1) indistinctly 4-segmented antennule in the female; (2) 5-segmented male antennule; (3) larger genital field in female; (4) inner long seta on P4 coxa; and (5) the morphology of caudal seta II, being long and plumose, with a bulbiform base in the female only.
www.zoobank.org/urn:lsid:zoobank.org:pub:33BFE1A2-8C95-4A9D-9E7A-B495CEEC3182 相似文献